The Impact of UFP-512 in Mice with Osteoarthritis Pain : The Role of Hydrogen Sulfide
Batallé Melgarejo, Gerard (Institut de Recerca Sant Pau)
Bai, Xue (Institut de Recerca Sant Pau)
Balboni, Gianfranco (Universitá di Cagliari. Dipartimento della Vita e dell'Ambiente)
Pol, Olga (Universitat Autònoma de Barcelona. Institut de Neurociències)

Fecha:	2023
Resumen:	The pain-relieving properties of opioids in inflammatory and neuropathic pain are heightened by hydrogen sulfide (HS). However, whether allodynia and functional and/or emotional impairments related to osteoarthritis (OA) could be reduced by activating δ-opioid receptors (DOR) and the plausible influence of HS on these actions has not been completely established. In female C57BL/6J mice with OA pain generated via monosodium acetate (MIA), we analyze: (i) the effects of UFP-512 (a DOR agonist), given alone and co-administered with two HS donors, on the symptoms of allodynia, loss of grip strength (GS), and anxiodepressive-like comportment; (ii) the reversion of UFP-512 actions with naltrindole (a DOR antagonist), and (iii) the impact of UFP-512 on the expression of phosphorylated NF-kB inhibitor alpha (p-IKBα) and the antioxidant enzymes superoxide dismutase 1 (SOD-1) and glutathione sulfur transferase M1 (GSTM1); and the effects of HS on DOR levels in the dorsal root ganglia (DRG), amygdala (AMG), and hippocampus (HIP) of MIA-injected animals. Results showed that systemic and local administration of UFP-512 dose-dependently diminished the allodynia and loss of GS caused by MIA, whose effects were potentiated by HS and reversed by naltrindole. UFP-512 also inhibited anxiodepressive-like behaviors, normalized the overexpression of p-IKBα in DRG and HIP, and enhanced the expression of SOD-1 and GSTM1 in DRG, HIP, and/or AMG. Moreover, the increased expression of DOR triggered by HS might support the improved analgesic actions of UFP-512 co-administered with HS donors. This study proposes the use of DOR agonists, alone or combined with HS donors, as a new treatment for OA pain.
Ayudas:	Instituto de Salud Carlos III PI18/00645 Instituto de Salud Carlos III PI21/00592
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Analgesia ; Antioxidants ; Anxiety ; Δ-opioid receptors ; Depression ; Osteoarthritis pain ; Oxidative stress
Publicado en:	Antioxidants, Vol. 12, Num. 12 (december 2023) , ISSN 2076-3921

DOI: 10.3390/antiox12122085
PMID: 38136204

16 p, 2.4 MB

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Documentos de investigación > Documentos de los grupos de investigación de la UAB > Centros y grupos de investigación (producción científica) > Ciencias de la salud y biociencias > Institut de Neurociències (INc)
Documentos de investigación > Documentos de los grupos de investigación de la UAB > Centros y grupos de investigación (producción científica) > Ciencias de la salud y biociencias > Institut de Recerca Sant Pau
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